CN112137976A - Aripiprazole sustained-release tablet and preparation method thereof - Google Patents
Aripiprazole sustained-release tablet and preparation method thereof Download PDFInfo
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- CN112137976A CN112137976A CN202011008167.4A CN202011008167A CN112137976A CN 112137976 A CN112137976 A CN 112137976A CN 202011008167 A CN202011008167 A CN 202011008167A CN 112137976 A CN112137976 A CN 112137976A
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- Prior art keywords
- aripiprazole
- release tablet
- sustained
- tabletting
- lactose
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- CEUORZQYGODEFX-UHFFFAOYSA-N Aripirazole Chemical compound ClC1=CC=CC(N2CCN(CCCCOC=3C=C4NC(=O)CCC4=CC=3)CC2)=C1Cl CEUORZQYGODEFX-UHFFFAOYSA-N 0.000 title claims abstract description 50
- 229960004372 aripiprazole Drugs 0.000 title claims abstract description 50
- 239000007939 sustained release tablet Substances 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title abstract description 19
- 238000000034 method Methods 0.000 claims abstract description 9
- 239000000463 material Substances 0.000 claims abstract description 8
- 239000000843 powder Substances 0.000 claims abstract description 7
- 239000000945 filler Substances 0.000 claims abstract description 5
- 239000000314 lubricant Substances 0.000 claims abstract description 5
- 239000001856 Ethyl cellulose Substances 0.000 claims description 13
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 13
- 229920001249 ethyl cellulose Polymers 0.000 claims description 13
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 13
- GUBGYTABKSRVRQ-QKKXKWKRSA-N lactose group Chemical group OC1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@@H](O)[C@H](O2)CO)[C@H](O1)CO GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 13
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 claims description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 11
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical group CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims description 11
- 229940049654 glyceryl behenate Drugs 0.000 claims description 11
- 239000008101 lactose Substances 0.000 claims description 11
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims description 11
- 229960004667 ethyl cellulose Drugs 0.000 claims description 9
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 8
- 229940075614 colloidal silicon dioxide Drugs 0.000 claims description 8
- 229960001375 lactose Drugs 0.000 claims description 8
- 238000007873 sieving Methods 0.000 claims description 5
- 239000008187 granular material Substances 0.000 claims description 4
- 239000008119 colloidal silica Substances 0.000 claims description 3
- 238000007908 dry granulation Methods 0.000 claims description 3
- 239000003826 tablet Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000003973 paint Substances 0.000 claims 1
- 239000002994 raw material Substances 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract description 8
- 239000012738 dissolution medium Substances 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 238000004090 dissolution Methods 0.000 description 9
- 238000009472 formulation Methods 0.000 description 6
- 239000007787 solid Substances 0.000 description 5
- 238000007907 direct compression Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000007547 defect Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- -1 2, 3-dichlorophenyl Chemical group 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 238000009702 powder compression Methods 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical class C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
- Psychiatry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to the field of medicines, in particular to an aripiprazole sustained-release tablet and a preparation method thereof. The invention discloses an aripiprazole sustained-release tablet and a preparation method thereof, wherein the aripiprazole sustained-release tablet comprises the following components in percentage by weight: 25-30% of aripiprazole, 30-40% of a filler, 25-40% of a framework material, 0.5-1% of a lubricant and 0.5-1% of a glidant. The aripiprazole and the auxiliary materials are uniformly mixed, and the aripiprazole sustained-release tablet is prepared by directly tabletting powder or granulating and tabletting by a dry method. The release rate of the aripiprazole is more than or equal to 80% within 4-5 hours by using 0.1M hydrochloric acid solution containing 2% SDS as a dissolution medium, and zero-order release can be achieved.
Description
Technical Field
The invention relates to the field of medicines, in particular to an aripiprazole sustained-release tablet and a preparation method thereof.
Background
Aripiprazole, chemical name 7- [4- [4- (2, 3-dichlorophenyl) -1-piperazinyl ] butoxy ] -3, 4-dihydro-2 (1 hydro) -quinolinone, molecular weight 448.39, is a quinolinone derivative that was approved by the U.S. FDA for marketing in 11 months of 2002, and is used for the treatment of schizophrenia.
Aripiprazole is a poorly soluble drug substance and when it is formulated into oral preparations such as tablets or other solid preparations including fast dissolving formulations, the dissolution characteristics of the resulting solid preparations are not ideal. In addition, the mechanical pulverization treatment of the aripiprazole is carried out by adopting a universal pulverizer to reduce the particle size so as to improve the dissolution, and the defects of much dust, environmental pollution, large loss and the like exist. In addition, when the aripiprazole solid preparation is prepared, the aripiprazole solid preparation prepared by a wet method has unsatisfactory stability, and related substances are easily generated. Therefore, there is a need to develop an aripiprazole formulation having good dissolution properties while avoiding the disadvantages of poor stability of the preparation process.
Disclosure of Invention
The invention aims to overcome the defects of poor stability and undesirable dissolution of a wet preparation method of an oral solid aripiprazole preparation, and provides an aripiprazole sustained-release tablet with good dissolution and a preparation method thereof.
The invention provides an aripiprazole sustained-release tablet which comprises, by weight, 25-30% of aripiprazole, 30-40% of a filler, 25-40% of a framework material, 0.5-1% of a lubricant and 0.5-1% of a glidant. The framework material is at least one of ethyl cellulose and glyceryl behenate, and the viscosity of the ethyl cellulose is 8-24 mPa.s, and more preferably 12-16 mPa.s; the filler is lactose, the lubricant is sodium stearyl fumarate, and the glidant is colloidal silicon dioxide.
The invention discloses a preparation method of aripiprazole sustained-release tablets, which comprises the steps of uniformly mixing aripiprazole and auxiliary materials, and preparing the aripiprazole sustained-release tablets by directly tabletting powder or tabletting by dry granulation.
When the aripiprazole and the auxiliary materials are subjected to a direct powder compression process, the method comprises the following steps: sieving aripiprazole, lactose, ethyl cellulose, colloidal silicon dioxide and glyceryl behenate with a 60-mesh sieve respectively, transferring the powder into a three-dimensional motion mixer, mixing at the speed of 12r/min for 20min, adding sodium stearyl fumarate, and continuously mixing for 3min, wherein the tabletting hardness is controlled to be 8-12 kg.
Adopts a dry method to granulate and tablet, and comprises the following steps: aripiprazole was mixed with colloidal silica and glyceryl behenate, rolled into a ribbon and granulated through a 1mm screen. Mixing the obtained granules with lactose, ethyl cellulose and sodium stearyl fumarate in a three-dimensional motion mixer at a speed of 12r/min for 10min, and controlling the tabletting hardness to be 8-12 kg.
The aripiprazole sustained-release tablet of the invention takes a 0.1M hydrochloric acid solution containing 2% SDS as a medium to investigate the dissolution performance, the release degree of the aripiprazole is more than or equal to 80% within 4-5 hours, and zero-order release is achieved.
Drawings
FIG. 1 dissolution Profile in 0.1M hydrochloric acid solution containing 2% SDS
Detailed Description
Example 1 formula and preparation method for aripiprazole sustained release tablet by powder direct compression method:
respectively sieving 28% aripiprazole, 36% lactose, 25% ethyl cellulose, 9% glyceryl behenate and 1% colloidal silicon dioxide with a 60-mesh sieve, mixing in a three-dimensional motion mixer at 12r/min for 20min, adding 1% sodium stearyl fumarate, mixing for 3min, and tabletting to obtain the aripiprazole sustained-release tablet with hardness of 8-12 kg.
Example 2 formula and preparation method for aripiprazole sustained release tablet by powder direct compression:
respectively sieving 30% aripiprazole, 40% lactose, 20% ethyl cellulose, 9% glyceryl behenate and 0.5% colloidal silicon dioxide with a 60-mesh sieve, mixing with a three-dimensional motion mixer at 12r/min for 20min, adding 0.5% sodium stearyl fumarate, mixing for 3min, and tabletting to obtain aripiprazole sustained-release tablets with hardness of 8-12 kg.
Example 3 formulation and preparation method for aripiprazole sustained release tablet by powder direct compression:
respectively sieving 28% aripiprazole, 30% lactose, 30% ethyl cellulose, 10% glyceryl behenate and 1% colloidal silicon dioxide with a 60-mesh sieve, mixing in a three-dimensional motion mixer at 12r/min for 20min, adding 1% sodium stearyl fumarate, mixing for 3min, and tabletting to obtain the aripiprazole sustained-release tablet with hardness of 8-12 kg.
Example 4 formula and preparation method for aripiprazole sustained release tablet by dry granulation and tabletting: aripiprazole 28% was mixed with colloidal silica 1% and glyceryl behenate 9%, rolled into a ribbon and granulated through a 1mm screen. Mixing the granules with 36% of lactose, 25% of ethyl cellulose and 1% of sodium stearyl fumarate in a three-dimensional motion mixer at a speed of 12r/min for 10min, and tabletting to obtain the aripiprazole sustained-release tablet with the hardness of 8-12 kg.
EXAMPLE 5 dissolution test
The dissolution performance of the aripiprazole sustained-release tablet is examined by taking 0.1M hydrochloric acid solution containing 2% SDS as a dissolution medium and taking three parts in parallel, the release rate of the aripiprazole within 4-5 hours is more than or equal to 80%, zero-order release is achieved, the results are shown in the following table, and the dissolution curve is shown in the attached figure 1 of the specification.
Claims (4)
1. An aripiprazole sustained-release tablet characterized by: the paint comprises the following components in percentage by weight: 25-30% of aripiprazole, 30-40% of a filling agent, 25-40% of a framework material, 0.5-1% of a lubricant and 0.5-1% of a flow aid;
the framework material is at least one of ethyl cellulose and glyceryl behenate, and the viscosity of the ethyl cellulose is 8-24 mPa.s, and more preferably 12-16 mPa.s;
the filler is lactose, the lubricant is sodium stearyl fumarate, and the glidant is colloidal silicon dioxide.
2. An aripiprazole sustained release tablet according to claim 1, wherein: comprises the following components in percentage by weight: 28% aripiprazole, 36% lactose, 25% ethylcellulose, 9% glyceryl behenate, 1% colloidal silicon dioxide, 1% sodium stearyl fumarate.
3. A process for preparing aripiprazole sustained-release tablets according to any one of claims 1-2, wherein: 1) the method adopts a powder direct tabletting process, prepares raw materials according to components and proportions, and comprises the following steps: sieving aripiprazole, lactose, ethyl cellulose, colloidal silicon dioxide, and glyceryl behenate with 60 mesh sieve, mixing with three-dimensional motion mixer at a speed of 12r/min for 20min, adding sodium stearyl fumarate, mixing for 3min, and tabletting. 2) Adopts a dry granulation and tabletting process, which comprises the following steps: aripiprazole was mixed with colloidal silica and glyceryl behenate, rolled into a ribbon, and granulated through a 1mm screen. Mixing the granules with lactose, ethyl cellulose and sodium stearyl fumarate in three-dimensional motion mixer at speed of 12r/min for 10min, and tabletting.
4. An aripiprazole sustained release tablet according to claim 3, wherein: the hardness of the pressed tablet is controlled to be 8-12 kg.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011008167.4A CN112137976A (en) | 2020-09-23 | 2020-09-23 | Aripiprazole sustained-release tablet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011008167.4A CN112137976A (en) | 2020-09-23 | 2020-09-23 | Aripiprazole sustained-release tablet and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112137976A true CN112137976A (en) | 2020-12-29 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011008167.4A Withdrawn CN112137976A (en) | 2020-09-23 | 2020-09-23 | Aripiprazole sustained-release tablet and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112137976A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080020038A1 (en) * | 2006-07-20 | 2008-01-24 | Helm Ag | Amorphous Aripiprazole and Process for the Preparation thereof |
| CN103462922A (en) * | 2012-06-06 | 2013-12-25 | 南京亿华药业有限公司 | Levetiracetam sustained release tablet and preparation method thereof |
-
2020
- 2020-09-23 CN CN202011008167.4A patent/CN112137976A/en not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080020038A1 (en) * | 2006-07-20 | 2008-01-24 | Helm Ag | Amorphous Aripiprazole and Process for the Preparation thereof |
| CN103462922A (en) * | 2012-06-06 | 2013-12-25 | 南京亿华药业有限公司 | Levetiracetam sustained release tablet and preparation method thereof |
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Application publication date: 20201229 |